| First Author | Adams JM | Year | 2018 |
| Journal | Cell Death Differ | Volume | 25 |
| Issue | 1 | Pages | 27-36 |
| PubMed ID | 29099483 | Mgi Jnum | J:268164 |
| Mgi Id | MGI:6269949 | Doi | 10.1038/cdd.2017.161 |
| Citation | Adams JM, et al. (2018) The BCL-2 arbiters of apoptosis and their growing role as cancer targets. Cell Death Differ 25(1):27-36 |
| abstractText | Impaired apoptosis plays a central role in cancer development and limits the efficacy of conventional cytotoxic therapies. Deepening understanding of how opposing factions of the BCL-2 protein family switch on apoptosis and of their structures has driven development of a new class of cancer drugs that targets various pro-survival members by mimicking their natural inhibitors, the BH3-only proteins. These 'BH3 mimetic' drugs seem destined to become powerful new weapons in the arsenal against cancer. Successful clinical trials of venetoclax/ABT-199, a specific inhibitor of BCL-2, have led to its approval for a refractory form of chronic lymphocytic leukaemia and to scores of on-going trials for other malignancies. Furthermore, encouraging preclinical studies of BH3 mimetics that target other BCL-2 pro-survival members, particularly MCL-1, offer promise for cancers resistant to venetoclax. This review sketches the impact of the BCL-2 family on cancer development and therapy, describes how interactions of family members trigger apoptosis and discusses the potential of BH3 mimetic drugs to advance cancer therapy. |
